What is the dosage and administration of Leukovorin (folinic acid) in chemotherapy regimens?

Leukovorin (Folinic Acid) Dosage and Administration in Chemotherapy Regimens

Leukovorin dosage in chemotherapy regimens varies by protocol, with standard doses ranging from 200-500 mg/m² IV depending on the specific regimen, with administration timing carefully coordinated with 5-FU or methotrexate administration to maximize efficacy and minimize toxicity. 1

Standard Dosing in Common Colorectal Cancer Regimens

FOLFOX Regimens

• FOLFOX 4:

  • Leucovorin 200 mg/m² IV over 2 hours, days 1 and 2
  • Followed by 5-FU 400 mg/m² IV bolus, then 600 mg/m² IV over 22 hours continuous infusion, days 1 and 2
  • Repeat every 2 weeks 1

• mFOLFOX 6:

  • Leucovorin 400 mg/m² IV over 2 hours, day 1
  • Followed by 5-FU 400 mg/m² IV bolus on day 1, then 1200 mg/m²/day × 2 days continuous infusion
  • Repeat every 2 weeks 1

FOLFIRI Regimen

• Leucovorin 400 mg/m² IV infusion to match duration of irinotecan infusion, day 1
• Followed by 5-FU 400 mg/m² IV bolus day 1, then 1200 mg/m²/day × 2 days continuous infusion
• Repeat every 2 weeks 1

FOLFOXIRI Regimen

• Leucovorin 400 mg/m² day 1
• With irinotecan 165 mg/m² IV day 1, oxaliplatin 85 mg/m² day 1
• Followed by fluorouracil 3200 mg/m² over 48-hour continuous infusion starting on day 1
• Repeat every 3 weeks 1

Bolus or Infusional 5-FU/Leucovorin Regimens

• Roswell-Park regimen:

  • Leucovorin 500 mg/m² IV over 2 hours, days 1,8,15,22,29, and 36
  • 5-FU 500 mg/m² IV bolus 1 hour after start of leucovorin
  • Repeat every 8 weeks 1

• Biweekly regimen:

  • Leucovorin 200 mg/m² IV over 2 hours, days 1 and 2
  • 5-FU 400 mg/m² IV bolus, then 600 mg/m² IV over 22 hours continuous infusion, days 1 and 2
  • Repeat every 2 weeks 1

• Simplified biweekly (sLV5FU2):

  • Leucovorin 400 mg/m² IV over 2 hours on day 1
  • Followed by 5-FU bolus 400 mg/m² and then 1200 mg/m²/day × 2 days continuous infusion
  • Repeat every 2 weeks 1

• Weekly regimen:

  • Leucovorin 20 mg/m² as a 2-hour infusion
  • 5-FU 500 mg/m² bolus administered 1 hour after LV infusion
  • Repeat weekly 1

Important Dosing Considerations

Levoleucovorin Equivalence

• Levoleucovorin dose is 200 mg/m², which is equivalent to leucovorin 400 mg/m² 1
• This equivalence must be considered when substituting between the two forms

Rectal Cancer-Specific Regimens

For concurrent chemotherapy/RT in rectal cancer:

• XRT + 5-FU/leucovorin:
  • 5-FU 400 mg/m² IV bolus + leucovorin 20 mg/m² IV bolus for 4 days during weeks 1 and 5 of XRT 1

Methotrexate Rescue

For high-dose methotrexate toxicity or delayed elimination:

• Start leucovorin rescue within 24 hours of methotrexate administration
• Initial dose: 15 mg (10 mg/m²) IM, IV, or PO every 6 hours until serum methotrexate level is less than 10⁻⁸ M
• If 24-hour serum creatinine increases 50% over baseline or if 24-hour methotrexate level is greater than 5 × 10⁻⁶ M (or 48-hour level is greater than 9 × 10⁻⁷ M), increase leucovorin to 150 mg (100 mg/m²) IV every 3 hours until methotrexate level is less than 10⁻⁸ M 2
• Doses greater than 25 mg should be given parenterally due to saturable oral absorption 2

Administration Pearls and Pitfalls

Key Administration Points

• Leucovorin should be administered before 5-FU in most regimens to optimize biochemical modulation
• For FOLFIRI, leucovorin infusion should match the duration of irinotecan infusion 1
• For methotrexate rescue, parenteral administration is preferred when GI toxicity, nausea, or vomiting is present 2

Potential Pitfalls to Avoid

• Oral absorption limitation: Oral administration of doses greater than 25 mg is not recommended due to saturable absorption 2
• Timing errors: Incorrect timing of leucovorin relative to 5-FU can reduce efficacy
• Dosing errors: NCCN recommends limiting chemotherapy orders to 24-hour units (i.e., 1200 mg/m²/day NOT 2400 mg/m²/day over 46-48 hours) to minimize medication errors 1
• Inadequate rescue: Insufficient leucovorin dosing in methotrexate toxicity can lead to severe complications
• Delayed rescue: Leucovorin rescue for methotrexate toxicity should begin as soon as possible and within 24 hours of methotrexate administration 2

Special Considerations

• Hydration (3 L/day) and urinary alkalinization with sodium bicarbonate should be employed concomitantly with leucovorin rescue for methotrexate toxicity 2
• Patients with delayed methotrexate elimination require continuing hydration, urinary alkalinization, and close monitoring of fluid and electrolyte status until serum methotrexate level falls below 0.05 micromolar 2
• Consider potential drug interactions that may interfere with methotrexate elimination or binding to serum albumin when laboratory abnormalities or clinical toxicities are observed 2